CA2243408C

CA2243408C - Sealing rubber closure for syringe/container

Info

Publication number: CA2243408C
Application number: CA002243408A
Authority: CA
Inventors: Masamichi Sudo; Morihiro Sudo
Original assignee: Daikyo Seiko Ltd
Current assignee: Daikyo Seiko Ltd
Priority date: 1997-03-12
Filing date: 1998-07-24
Publication date: 2005-05-24
Anticipated expiration: 2018-07-24
Also published as: EP0974372B1; US7214214B2; EP0974372A1; JP3380705B2; US20020022809A1; US6344034B1; JPH10248929A; CA2243408A1; US20030094429A1; US6524282B1

Abstract

A sealing rubber closure is provided for use with a syringe/container specified by ISO (the International Organization of Standardization) and having a Luer nozzle to be inserted into a Luer-nozzle-receiving part of the sealing rubber closure. The Luer-nozzle-receiving part is configured, on a side of an inner end portion thereof, in an untapered cylindrical form to assure tight-fitted insertion of a free end portion of the Luer nozzle and, on a side of a Luer-nozzle-receiving opening thereof, in a tapered, substantially cylindrical form to assure tight-fitted insertion of a basal end portion of the Luer nozzle. A plastic film is laminated on the sealing rubber closure at least in an area of the Luer-nozzle-receiving part, where a free end of the Luer nozzle is to be maintained in contact with the sealing rubber closure. The sealing rubber closure can exhibit both excellent liquid leakproofness and superb gas sealing performance. The sealing rubber closure can avoid any contact with a liquid medicine so that it does not give any adverse effects to a liquid medicine filled in the syringe/container.

Description

SEALING RUBBER CLOSURE FOR SYRINGE/CONTAINER
BACKGROUND OF THE INVENTION
a) Field of the Invention The present invention relates to a rubber-made sealing closure (which may also be called a "rubber cap" or "rubber closure") adapted to be fitted on a liquid-medicine-injecting port (Luer nozzle) of a syringe/container with a medicament contained therein to so that a solid or liquid injectable preparation con-tained as the medicament in the syringe/container can be sealed in place to maintain its quality over an ex-tended period of time. The sealing closure has a plastic film laminated thereon at least at an area of an inner wall thereof, where the sealing closure is to be brought into or maintained in contact with the solid or liquid injectable preparation.
b) Description of the Related Art For medicament containers, especially containers 2o for injectable preparations, strict sealing performance is specified and required as their function in the Pharmacopoeia, to say nothing of the quality of the container material. Accordingly, rubber-made sealing closures in the form of single pieces of rubber without any plastic film laminated thereon have been used be-cause they are considered to be the best in sealing performance.
On the other hand, rubber-made caps which are used with syringes as medical devices are different from sealing rubber closures employed with general con-tainers for injectable preparations such as vials in that the sealing rubber closures normally remain in contact with liquid medicines (the Pharmacopoeia specifies certain quality standards required for the sealing rubber closures).
It is indicated that, when new drugs of these days are brought into direct contact with a rubber material, their active ingredients undergo modifica-tions, thereby making it difficult to maintain their stability over an extended period of time.
Sealing rubber closures for syringe/containers with medicaments filled and sealed therein in advance (which will hereinafter be called "prefilled syringes"
on the authority of ISO 11040-1 and the like) are most-ly made of a rubber material alone.
An injectable liquid preparation, which has been formulated in a form filled and sealed in a prefilled syringe, always remains in contact with a sealing rub-ber closure as opposed to an active ingredient in a medicinal preparation contained in a vial (a vessel of small capacity), so that the active ingredient in the injectable liquid preparation in the prefilled syringe tends to receive greater chemical influence from the rubber closure. From the standpoint of protection of the active ingredient from contamination, the condi-tions under which the active ingredient is placed are severe.
Concerning prefilled syringes themselves, a vari-ety of proposals have been made to date for example, in JP kokai 7-313598 (syringe-shaped container), JP kokai 8-280800 (prefilled syringe for two-part injectable preparation), JP kokai 8-317975 (prefilled syringe and a stopper assembly therefor), and EP 07 09 105A
(prefilled syringe and production process of the same).
These publications all disclose the structures and function of prefilled syringes, but make no mention whatsoever about the quality and function of sealing rubber closures employed for the sealing of the prefilled syringes.
In connection with rubber closures, on the other hand, the present assignee disclosed in JP kokai 62-139668 (laminated plug for syringe) various examples of rubber-made sliding plugs (plungers) for prefilled syringes, said plugs being laminated at surfaces there-of with tetrafluoroethylene-ethylene copolymer films, and one example of a rubber plug for a front end por-tion of a syringe (see Fig. 9 in the kokai publication;
Fig. 2A in this application). The rubber plug for the front end portion of the syringe, which is disclosed by way of example in the kokai publication, is indicated to be kept out of contact with a liquid medicine owing to the laminated film. Its Luer-nozzle-receiving part (a part in which a liquid-medicine-injecting port is inserted) is however configured in a substantially cylindrical, tapered form (i.e., the diameter on a side of an inner end portion is smaller than the diameter on a side of a Luer-nozzle-receiving opening). According-ly, the Luer nozzle tends to fall out and sealing per-formance is hardly available, although the Luer-nozzle-receiving part is formed with an average outer diameter smaller than that of the associated Luer nozzle.
With a view. to overcoming this problem, the pres-ent inventors attempted to close a free end aperture of the Luer nozzle by forming the Luer-nozzle-receiving part of the rubber closure into an untapered cylindri-cal form (the diameter of which was smaller than the maximum diameter of the Luer nozzle) as shown in Fig.
2B and then forming a small bead on an inner end wall of the Luer-nozzle-receiving part as depicted in Fig.
2C. However, the insertion of the Luer nozzle was not smoothly performed and, when the Luer nozzle was in-serted, wrinkles were developed in the laminated film, thereby failing to obtain satisfactory sealing per-formance.
As has been described above, the conventionally proposed sealing rubber closures in which the front ends of syringes are to be inserted have fluorinated resin films laminated on inner walls thereof, so that the rubber closures are maintained out of direct con-l0 tact with their corresponding liquid medicines. Since a fluorinated resin has high stiffness and can be hard-ly deformed, it must inherently apply high fastening force to the Luer nozzle inserted in the rubber closure. However, the inner wall of the rubber closure is formed in a substantially cylindrical form which has substantially the same taper as the Luer nozzle, and the fluorinated resin has small frictional resistance with other materials. Especially in the case of a plastic-made syringe, the inserted Luer nozzle there-fore tends to slide. Compared with a rubber closure not laminated with a fluorinated resin film, the rubber closure with the fluorinated resin film laminated thereon is inferior in sealing performance. Therefore, the rubber closure with the fluorinated resin film laminated thereon is not suited for practical use and requires improvements in sealing performance. If the Luer-nozzle-receiving part of the rubber closure is configured in an untapered cylindrical form, on the other hand, the Luer nozzle cannot be inserted smooth-y ly, and wrinkles are hence formed in the laminated film, thereby failing to obtain satisfactory sealing performance.
SUMMARY OF THE INVENTION
With the foregoing circumstances in view, the present inventors have proceeded with an extensive in-vestigation to develop a rubber closure for a prefilled syringe, which has new configurations and function and carries a fluorine resin film or the like laminated on an inner wall thereof so that excellent sealing per-formance can be achieved like conventional rubber closures without laminated films and any direct contact between a liquid medicine and the material of the rub-ber closure can be avoided. This investigation has resulted in the completion of the present invention.
To achieve the above object, the present inven-tion provides a sealing rubber closure for use with a prefilled syringe specified by ISO (the International Organization of Standardization) and having a Luer nozzle to be inserted into a Luer-nozzle-receiving part of the sealing rubber closure, wherein the Luer-nozzle-receiving part of the sealing rubber closure is con-figured, on a side of an inner end portion thereof, in an untapered cylindrical form to assure tight-fitted insertion of a free end portion of the Luer nozzle and, on a side of a Luer-nozzle-receiving opening thereof, in a tapered, substantially cylindrical form to assure tight-fitted insertion of a basal end portion of the Luer nozzle, and a plastic film is laminated on the sealing rubber closure at least in an area of the Luer-nozzle-receiving part, where a free end of the Luer nozzle is to be maintained in contact with the sealing rubber closure.
The present invention also provides a sealing rubber closure similar to the above-described sealing rubber closure, which is for use with a prefilled syringe specified by ISO (the International Organiza-tion of Standardization) and having a Luer nozzle and a Luer lock.
According to the present invention, each of the sealing rubber closures, in which a liquid-medicine-injecting portion such as the Luer nozzle of the prefilled syringe is to be inserted, can exhibit both excellent liquid leakproofness and superb gas sealing performance even when its receiving part, where the g -liquid-medicine-injecting portion is received, is laminated over the entire inner wall thereof with a plastic film.
Similarly to various conventional rubber closures laminated at liquid-medicine-contacting portions there-of with plastic films, the sealing rubber closures ac-cording to the present invention can avoid any contact with a liquid medicine so that they do not give any ad-verse effects to the liquid medicine.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and other objects, features and ad-vantages of the present invention will become apparent from the following description and the appended claims, taken in conjunction with the accompanying drawings, in which:
Fig. lA is a schematic cross-sectional view of a prefilled syringe having only a Luer nozzle;
Fig. 1B is a schematic cross-sectional view of a prefilled syringe having a Luer nozzle and a Luer lock;
Fig. 1C is a perspective view of the Luer nozzle and Luer lock of the prefilled syringe shown in Fig.
1B;
Fig. 2A is a schematic cross-sectional view of a conventional rubber closure;

_ g -Fig. 2B is a schematic cross-sectional view of another conventional rubber closure;
Fig. 2C is a schematic cross-sectional view of a further conventional rubber closure;
Fig. 3A is a schematic cross-sectional view of a sealing rubber closure according to one embodiment of the present invention;
Fig. 3B is a schematic cross-sectional view of a sealing rubber closure according to another embodiment of the present invention;
Fig. 3C illustrates the sealing rubber closure of Fig. 3B with a Luer nozzle of a prefilled syringe in-serted therein;
Fig. 4A is a schematic cross-sectional view of a sealing rubber closure according to a further embodi-ment of the present invention;
Fig. 4B is a schematic cross-sectional view of a sealing rubber closure according to a still further em-bodiment of the present invention;
Fig. 5A is a schematic cross-sectional view of a sealing rubber closure according to a still further em-bodiment of the present invention;
Fig. 5B is a schematic cross-sectional view of a sealing rubber closure according to a still further em-bodiment of the present invention;

Fig. 6A is a schematic cross-sectional view of a sealing rubber closure according to a still further em-bodiment of the present invention;
Fig. 6B illustrates the sealing rubber closure of Fig. 6A with a Luer nozzle and Luer lock of a prefilled syringe inserted therein;
Fig. 7 is a schematic cross-sectional view of a sealing rubber closure according to a still further em-bodiment of the present invention; and Fig. 8 is a schematic cross-sectional view of a sealing rubber closure according to a still further em-bodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
AND PRE~ER~D EMBODIMENTS
With reference to the accompanying drawings, the present invention will hereinafter be described more specifically on the basis of its preferred embodiments.
Schematic cross-sectional views of examples of syringe/containers (prefilled syringes) to which seal-ing rubber closures according to the present invention are applied are shown in Fig. 1A and Fig. 1B, respec-tively. Namely, the sealing rubber closures according to the present invention can be applied to a prefilled syringe provided with only a Luer nozzle 2 arranged as a liquid-medicine-injecting portion on a front end wall of the prefilled syringe (Fig. lA) or to a prefilled syringe provided on a front end wall 5 thereof with a Luer nozzle 2 and a Luer lock 3 for firmly fixing an 5 extension tube, a three-way cock or the like on the prefilled syringe without becoming loose (Fig. 1B, and Fig. 1C which is a perspective view of the Luer nozzle and Luer lock). These prefilled syringes are generally made of plastics.
The shapes and dimensions of the Luer nozzle 2 and the Luer lock 3 in the prefilled syringes are specified by ISO Standards (for example, ISO 594-2, etc.).
In the case of the prefilled syringe shown in Fig. 1B and having the Luer nozzle 2 and the Luer lock 3, for example, the Luer nozzle 2 which is arranged in the form of a hollow cylinder on the front end wall 5 of a syringe barrel 1 is configured to have an about 6/100 taper so that its outer diameter is smaller at a free end portion thereof than at a basal end portion thereof. The Luer lock 3 is in the form of a cylinder arranged concentrically on an outer side of the Luer nozzle 2 and has a helical groove (not shown) formed on an inner wall thereof. An injection needle or the like is screwed in a space 6 between the Luer nozzle 2 and the Luer lock 3 so that the injection needle or the like is maintained in engagement with the prefilled syringe. The length of the Luer nozzle 3, the length and inner diameter of the Luer lock 3, and the like are standardized by ISO.
The Luer nozzle 2 is tapered on a peripheral wall thereof as described above. In the conventional seal-ing rubber closure 9 shown in cross-section in Fig. 2A, a Luer-nozzle-receiving part 11 is therefore configured in a substantially cylindrical form having a slight taper (its average bore diameter is smaller than an average outer diameter of the Luer nozzle), and is laminated with a plastic film 10 such as a fluorinated resin film to avoid any direct contact with a medica-ment. Compared with a rubber material, a fluorinated resin has higher stiffness and is hence more resistant to deformation. For its smaller frictional resistance with other materials, however, the tapered Luer nozzle inserted in the sealing rubber closure tends to fall out. It is therefore difficult to maintain sealing performance with a rubber closure laminated with a fluorinated resin film.
When, as is illustrated in Fig. 2B, the receiving part 11 is configured in an untapered cylindrical form having a diameter smaller than the average outer diameter of the Luer nozzle 2 with a view to assuring tight-fitted insertion of the Luer nozzle, the inser-tion of the Luer nozzle cannot be performed smoothly, resulting in the development of wrinkles in the laminated film and the failure to obtain sealing per-formance as described above.
Each rubber closure according to the present in-vention for being fitted on a Luer nozzle of a prefilled syringe to seal the syringe (which will hereinafter be called simply a "rubber closure") can improve the above-described drawbacks of the conven-tional rubber closures.
A principal feature of each rubber closure ac-cording to the present invention resides in that, as is depicted in Fig. 3A through Fig. 4B, a Luer-nozzle-receiving part of the rubber closure 9 is configured in an untapered cylindrical form on a side of an inner end portion thereof (in an upper portion thereof as viewed in the corresponding drawing) and in a tapered, sub-stantially cylindrical form on a side of a Luer-nozzle-receiving opening thereof (in a lower portion thereof as viewed in the corresponding drawing).
The diameter of the Luer-nozzle-receiving opening of the rubber closure 9 is greater than the outer diameter of the free end portion of the Luer nozzle, and the Luer-nozzle-receiving part is configured in the appropriately-tapered cylindrical form to a certain depth from the Luer-nozzle-receiving opening. Accord-ingly, the insertion of the Luer nozzle into the rubber closure can be performed easily and smoothly while avoiding development of wrinkles in the film laminated on the inner wall of the rubber closure. Further, the Luer-nozzle-receiving part is formed, on the side of the inner end portion thereof, in the untapered cylindrical form the inner diameter of which is smaller than the average outer diameter of the free end portion of the Luer nozzle. Excellent sealing performance can therefore be maintained.
Concerning rubber closures according to the pres-ent invention, a description will first be made about those applied to prefilled syringes liquid-medicine-injecting portions of which consist of Luer nozzles alone. One example of such rubber closures according to the present invention will be described with reference to Fig. 3A, which is its schematic cross-sectional view. A Luer-nozzle-receiving part 11 of the rubber closure 9 is configured, on the side of its in-ner end portion (the portion above the broken line), in an untapered cylindrical form the diameter of which is smaller than the average outer diameter of the free end portion of the Luer nozzle, said free end portion being to be inserted in the inner end portion, so that the Luer nozzle can be inserted there in a tight-fitted manner. The remaining portion (the portion below the broken line) is configured in a tapered, substantially cylindrical form the average bore diameter of which is somewhat smaller than the average outer diameter of the remaining portion of the Luer nozzle, said remaining portion being to be inserted in the former remaining portion, for example, by about 5 to 30~. Further, A
plastic film 10 is laminated at least on the inner end wall of the Luer-nozzle-receiving part, with which the free end of the Luer nozzle will be maintained in con-tact. From the standpoint of the production of the rubber closure, it is generally preferred to laminate such a plastic film on the entire inner wall of the Luer-nozzle-receiving part. This will apply equally to the rubber closures according to the other embodiments of the present invention, which will be described sub-2o sequently herein.
As the inner diameter of the Luer-nozzle-receiving opening of the rubber closure according to the present invention is formed greater than the outer diameter of the free end of the Luer nozzle as de-scribed above, the insertion of the Luer nozzle into _ 1. 6 the Luer-nozzle-receiving opening ~war~ be facilitated and, when the Luer nozzle :is inserted, no wrinkles are developed in the 3.aminated film. To further facilitate the insertion c:~:~ t.h~~. bust nozzle a: into the Luer-nozzle-receiving opening lla, it is preferred to round an :inner pex:ipheral edge portion of the lower end portion 13, in other words, near the opening lla of the Lue~r~-r~ozri.e--receiving part: 11 as shown in Fig. 3B.
Incidentally, the '"taper~ld, substantially cylindrical form" can be embodied in two ways in the present invention, one being tt3.e case in whic::h the dif-ference between the bore diameter of the cylindrical Luer-nozzle-receiving parwt nrx t:he side of the inner end portion thereof and that of the. Luer-nozzle-receiving part on the side of the Luer-nozzle-receiving opening thereof is small, and the othex° being the case in which the degree of tapering of the Luer-nozzle-receiving part on the side of the Luer-nozzle-receiving opening is set so that the space of the Luer-nozzle-receiving part takes the form of a combined shape of a frustum of a right circular cone and a right circular cylinder.
The expression "tapered, substantially cylindrical form" is used in such a sense as embracing these two cases. This meaning will apply equally to the other rubber closures of the present invention to be de-scribed subsequently herein.
Further, the expression "tight-fitted insertion"
as used herein means that, as is apparent from the foregoing description, an inserted Luer nozzle or, in the rubber closures of the other embodiments to be des-cried subsequent herein, an inserted Luer lock is firm-ly fastened by compressive force from a Luer-nozzle-receiving part or Luer-lock-receiving part. This mean-ing will apply equally to the other rubber closures of the present invention.
The untapered cylindrical portion (the portion above the broken line in Fig. 3A or Fig. 3B) of the Luer-nozzle-receiving part 11 has dimensions (length or depth) sufficient to receive at least 30%, preferably 40 to 90%, more preferably 40 to 800 of the length of the Luer nozzle, and the remaining portion (the portion below the broken line in Fig. 3A or 3B) of the Luer-nozzle-receiving part 11 is formed in the tapered, sub-stantially cylindrical form.
No particular limitation is imposed on the degree of tapering of the tapered portion of the Luer-nozzle-receiving part (the bore diameter of which is smaller on the side of the inner end portion than on the side of the Luer-nozzle-receiving opening), insofar as the insertion of the Luer nozzle is facilitated. The de-gree of tapering varies depending on the percentage of the Luer nozzle to be inserted in the Luer-nozzle-receiving part, the percentage of the tapered portion based on the Luer-nozzle-receiving part, the hardness and thickness of the rubber closure, and so on, and can be hardly determined in a wholesale manner. An optimal degree of tapering, therefore, has to be determined by a trial and error method while taking these factors in consideration.
To increase the fastening force for the Luer nozzle so that the sealing performance can be heightened, it is preferred to form at least a portion of the Luer-nozzle-receiving part of the rubber closure, preferably a portion of the rubber closure, said portion extending to at least one fourth (1/4), more preferably from one third (1/3) to a half (1/2) of the overall length of the rubber closure from the lower end of the rubber closure, more resistant to deforma-tion than the remaining portion thereof.
No particular limitation is imposed on the ex-ternal appearance or shape of each rubber closure ac-cording to the present invention, but a cylindrical or frustoconical (which means a frustum of a circular cone) shape is preferred from the standpoint of isotropically fastening a Luer nozzle inserted in its Luer-nozzle-receiving part. The subsequent description on the wall thickness will be made based on these shapes.
No particular limitation is imposed on the method for making the lower end portion of the rubber closure more resistant to deformation than the remaining por-tion. As is depicted at numeral 12 in Fig. 3B, for ex-ample, it may be mentioned, as a simple method, to make the wall thickness greater on the side of the lower end of the rubber closure than the remaining portion of the rubber closure. In general, the preferred average wall thickness of the Luer-nozzle-receiving part 11 may range from 50 to 150% of the average outer diameter of the Luer nozzle, and the preferred average wall thick-ness of the Luer-nozzle-receiving part 11 on the side of the lower end of the rubber closure may be at least 10%, preferably 30 to 200%, more preferably 50 to 150%
greater than the average wall thickness of the Luer-nozzle-receiving part. An increase in the wall thick-ness by less than 10% cannot bring about any substan-tial change in sealing performance. On the other hand, even an increase in the wall thickness by more than 200% cannot improve the sealing performance further so that such an excessively large wall thickness is not economical. Incidentally, the portion of such an in-creased wall thickness extends over the above-described range from the lower end of the rubber closure. On a part of this portion, an annular flange of a desired shape such as a semicircular or quadrilateral shape in cross-section may be formed as shown in Fig. 4A. In this modification, the Luer-nozzle-receiving part may be provided with a similar bulged annular portion on the inner wall thereof at a location corresponding to the above-described annular flange.
From the standpoint of further heightening the sealing performance of the rubber closure, it is preferred to determine the wall thickness of the Luer-nozzle-receiving part as described above and further to control the hardness (JIS A hardness) of the rubber closure within a range of from 40 to 70, desirably from 55 to 70.
The Luer-nozzle-receiving part 11 of the rubber closure is generally formed with a length (depth) suf-ficient to permit the insertion of 50% or more of the Luer nozzle. When it is formed with a depth sufficient to receive the Luer nozzle in its entirety, the Luer-nozzle-receiving opening (lower end) of the rubber closure is brought into contact at least at the inner peripheral edge portion thereof with the front end wall 5 of the prefilled syringe. The lower end of the rub-ber closure is generally configured in the form of a horizontal surface as depicted in Figs. 2A to 2C. To heighten the sealing performance, however, it is preferred to configure the Luer-nozzle-receiving open-s ing of the rubber closure into a shape (surface) com-elementary with the basal portion of the Luer nozzle or the surrounding front end wall (5 in Fig. 1B), with which the Luer-nozzle-receiving opening is to be brought into contact, as indicated at numeral 13 in Fig. 3B so that, when the Luer nozzle has been in-serted, the lower end surface 13 can be maintained in close contact with the front end wall 5. Even when the length (depth) of the Luer-nozzle-receiving part 11 of the rubber closure is dimensioned shorter (shallower) than the overall length of the Luer nozzle and the lower end of the Luer-nozzle-receiving part is con-figured in the form of a horizontal surface, it is preferred to provide the inner peripheral edge portion of the lower end of the rubber closure with an ade-quately rounded portion 13 (Fig. 3A) so that the inser-tion of the Luer nozzle can be facilitated.
The rubber closures illustrated in Fig. 3A
through Fig. 4B are examples of the construction that the Luer-nozzle-receiving part 11 of each rubber closure 9 is formed to a depth sufficient to receive the Luer nozzle over the entire length thereof and is configured in a untapered cylindrical form in a portion thereof extending over 60~ the way down from the inner end portion thereof and in a tapered, substantially cylindrical form in the remaining portion thereof, the entire inner wall of the Luer-nozzle-receiving part and the peripheral edge wall of the Luer-nozzle-receiving opening are entirely laminated with a plastic film, and the Luer-nozzle-receiving opening of the rubber closure (see Fig. 3B, Fig. 4A and Fig. 4B) is configured in a shape maintainable in close contact with the front end wall 5 of the prefilled syringe. In these examples, the wall thickness of the Luer-nozzle-receiving part is made greater within the above-descried range in a por-tion thereof extending over 40~ the way up from the Luer-nozzle-receiving opening (the portions indicated at numeral 12 in Fig. 4A and Fig. 4B) than the remain-ing portion of the Luer-nozzle-receiving part.
A description will next be made about rubber closures according to the present invention, which are suited for use with prefilled syringes liquid-medicine-injecting portions of which are each composed of a Luer nozzle and a Luer lock.
One example of the rubber closures will be de-scribed based on Fig. 5A which illustrates it in cross-section.
A receiving part of the rubber closure 9 is com-posed of a Luer-nozzle-receiving part 11 and a Luer-lock-receiving part 14. The Luer-nozzle-receiving part 11 has a depth sufficient to permit the insertion of the Luer nozzle over the entire length thereof (i.e., the entirety of the portion protruding from the free end of the Luer lock), and is configured in an un-tapered cylindrical form having a bore diameter smaller than the average outer diameter of the Luer nozzle at a corresponding location, for example, by about 5 to 30%.
On the other hand, the Luer-lock-receiving part 14 is configured at a portion thereof, which extends over at least 10%, preferably 10 to 40% (to the extent up to the broken line) of the overall length of the Luer-lock-receiving part from a receiving opening of the receiving part of the rubber closure, in a tapered, substantially cylindrical form having an average bore diameter smaller than the outer diameter of the Luer lock to be inserted in the portion, for example, by about 5 to 30%. The remaining portion (the portion above the broken line) of the Luer-lock-receiving part is configured in an untapered cylindrical shape having a bore diameter smaller than the outer diameter of the Luer lock, for example, by about 5 to 30%.

In general, the outer diameter of the Luer lock is about 5 times as large as the average outer diameter of the Luer nozzle. Unless the degree of the above-described tapering is set equal to or greater than the degree of tapering of the outer peripheral surface of the Luer nozzle, the insertion of the Luer lock is therefore hampered so that a laminated film 10 may be caused to develop wrinkles. On the other hand, no par-ticular limitation is imposed on the degree of tapering insofar as it facilitates the insertion of the Luer lock into the Luer-lock-receiving part. The degree of tapering varies depending on the length of a portion which is provided with a taper. It is necessary to in-crease the degree of tapering as the length of the tapered portion becomes shorter. Further, the degree of tapering also varies depending on the hardness and wall thickness of the rubber closure, that is, the ease of deformation.
It is thus extremely difficult to specify an op-timal degree of tapering in a wholesale manner. An op-timal degree of tapering, which facilitates the inser-tion of the Luer lock into the receiving opening and also assures close contact with the Luer lock after the insertion, must be determined by a trial and error method while taking the above-described factors into ~5 _ cons iderat:ion .
The preferred wall thickness of the Luer-lock-receiving part 1.4 may be from :~0 to 100%, more preferably' from 40 to E30~ of the outer diameter of the Luer lock. Due to thc~ shape of' the rubber closure ac-cording to the embodiment, the wall thickness of the Luer-nozzle-receiving part 11 unavoidably becomes sub-stantially greater than the wall thickness of the Luer-lock-receiving part 14.
In addition, the recei~ri.r~g part of the rubber closure according to his embodiment is laminated with the plastic film 10 at Least in an area where the free end of the: Luer nozzle is braught into contact with the rubber closure. Laminated locations arc3 the same as those of the rubber closures described above.
In Fig. 5A, the lower end 13 (near the receiving opening 16? of the rubbfer closure ~ is configured in the foam of a ho:r~izc;>ntal surface. To facilitate the insertion of t.~na I:auer lock 3, it is preferred to provide, as shown ir1 Fag. 5B, the peripheral edge portion c~f the recweiving opening 16 of the rubber closurE= wit.~a an :adequate rounded portion 1:3, for exam~ale, a roundec portion similar to the rounded portion in tree °,ri~::i.nzty of the basal portion of the Luer lock. To :~~eir~hten the sealing performance further, it i.s pr+~fera:-ed., as is il~-.- ~C~
lustrated in Fig. SB,. t.o c?anf:ir:~ur~~ the lower end 13 (near the receiving open:i.ng 1 ~ z 1a of. the Luer~-lock-receiving part in a shape main~:air~able in close contact with the front. end wal:~ of the prefilled syringe and/or the basal part_i:~n <af the Luer lock 3 as in the ease of the rubber ~:vlos~.~res 9 described above. Tnsofar as the lower ~~~nd c.>f the rubber closure 9 is configured in a shape maintainable in close contact with the front end wall or the like of the prefilled syringe 8, tine insertion of the Luer lock into the Luer-~:~.ock-r~:ceirring opening can be carried out smoothly with extreme ease even if the Luer-lock-°receiving part l4 ~.s configured as a whole in an untapered cylindrical form as is depicted in Fig. 7.
This makes it possible to avoid de~relopment of wrinkles Z5 in the laminated film and hence to obtain high sealing performance. Fig. 5B illustrates an example in which the Luer-lock-receiving part 14 is configured as a whole in an untapered cylindrical form.
To further heighten the sealing performance, it is preferred to make at least, a portion of the Luer-lock-receiving part 14, said portion extending preferably to at least: one fourth (l/~), more preferab-ly to one third (1/3) of the overall length of the rub-ber closure from the lower end of the rubber closure, more resistant to deformation than the remaining por-tion thereof.
No particular limitation is imposed on the method for making the above-mentioned portion more resistant to deformation, but a preferred method is similar to the preferred method described above in connection with the rubber plugs of Fig. 3A to Fig. 4B. Namely, it is preferred to make the wall thickness of the above-mentioned portion greater by at least 5%, preferably l0 to 200%, more preferably 40 to 150% than the above-described average wall thickness of the Luer-lock-receiving part 14. An increase in the wall thickness by less than 5% cannot bring about any substantial im-provement in sealing performance. On the other hand, even an increase in the wall thickness by more than 200% cannot bring about any additional improvement in sealing performance so that such an excessively large wall thickness is not economical.
In addition, it is also preferred, from the standpoint of heightening sealing performance, to make the hardness of the rubber closure similar to that of the rubber closures described above with reference to Fig. 3A through Fig. 4B.
In Fig. 6A and Fig. 6B, further examples of rub-ber closures of this invention for use with prefilled syringes having Luer locks are illustrated in cross-_ 28 -section. Different from the rubber closures shown in Fig. 5A and Fig. 5B, a cylindrical ridge 15 is formed on the side of the inner end portion of the receiving part of a rubber closure 9. The cylindrical ridge is to be inserted in a tight-fitted state not only in a Luer-nozzle-receiving part 11 and a Luer-lock-receiving part 14 but also in an annular space (6 in Fig. 1B) be-tween the Luer nozzle and the Luer lock. Except for the cylindrical ridge, the rubber closure has the same structure as the rubber closure of Fig. 5A or Fig. 5B.
Namely, the space of the Luer-lock-receiving part 14 can be configured in a partly-tapered cylindrical form as in Fig. 5A (Fig. 6A) or in a fully untapered cylindrical form as illustrated in Fig. 5B (Fig. 6B).
From the standpoint of sealing performance, it is preferred to make the thickness of the cylindrical ridge 15, which is to be inserted in the annular space, greater, for example, by 5 to 20% than the average width of the annular space 6 of the prefilled syringe (see Fig. 1C). The height (length) of the cylindrical ridge 15 may be set at a value sufficient to reach the bottom of the annular space 6, or may be set at such a value that the cylindrical ridge extends only to an in-termediate height of the annular space 6. In the lat-ter case (Fig. 6B), it is preferred, for heightened sealing performance, to set the height (length) of the cylindrical ridge 15 at a value equivalent to at least 20~ of the depth of the annular space 6.
In the rubber closure shown in Fig. 6A, it is also preferred to provide an inner peripheral edge por-tion of a Luer-lock-receiving opening with a rounded portion similar to that formed in the vicinity of the basal portion of the Luer nozzle so that the rubber closure can be maintained at the inner peripheral edge portion of the lower end thereof in close contact with a basal portion of the Luer lock.
A still further embodiment of the present inven-tion is depicted in Fig. 7. A rubber closure 9 of this embodiment, which is for use with a prefilled syringe having a Luer nozzle and Luer lock to be inserted in the rubber closure, is configured, at a wall 13 sur-rounding a Luer-lock-receiving opening of a Luer-lock-receiving part 14 of the rubber closure, in a form maintainable in close contact with the basal portion of the Luer lock and a wall of the syringe, said wall sur-rounding the basal portion of the Luer lock, and the Luer-lock-receiving part 14 is configured as a whole in an untapered cylindrical form.
A still further embodiment of the present inven-tion is shown in Fig. 8. A rubber closure 9 of this -. 3 C
embodiment, which is for ~.rse with a prefilled syringe having a Luer nozzle to k7e irnserted in the rubber closure, is configured, at a wall. 1~ surrounding a Luer-nozzle-receiving apen~ng of a Luer-nozzle-receiving part 11 of the rubbex° closure, in <x form maintainable in cl.ase contacta with the basal pardon of the Luer nozzle and a wall of the syringe, s<~id wall surrounding the basal portion csf the Luer nozzle, and the Luer-nozzle-receiving parfi: 11 is configured as a whole in an untapered cylindrical form.
In each of the a:k~ove-~descxibed rubber closures 9, a plastic film is :~.G~mi.nated ran at least a portion of its Luer-nozzle-re~::ei.va.ng part 11, which is adapted to receive a 2:x:ee~ end pr~rtir~n of. a Luer nozzle of a pre-fille~~i syringe 8 and may be k>rought into direct contact with <~ liduid medicine 7 or the like filled in the prefil.led syx~ingea No paxaicular limitation is imposed an an area or areas to be laminated other than the above-described laminated portion. A plastic: film :LO rnay be laminated on the entire inner wall rrf the rec:eivi.ng part 11 ax: 14 and/or on the peripheral edge portion 13 of t:he receiving opening lla r~r 1~-~ .
The above-described rubber closures of this in-vention can be produced using a rubber material, a vul-canizer and other additives, which have been used to date for the production of rubber closures for vials.
As the liquid medicine filled in the prefilled syringe and the rubber closure are prevented from undergoing direct contact owing to the provision of the plastic film, the liquid medicine is free from the potential danger that it could be contaminated by a substance eluted from the rubber closure. No limitation is therefore imposed on the kinds, amounts and the like of the rubber material and additives.
Examples of the rubber material can include, but are not limited to, natural rubber (NR), polyisoprene rubber (IR), polybutadiene rubber (BR), styrene-butadiene copolymer rubber (SBR), butyl rubber (IIR), divinylbenzene-copolymerized butyl rubber (XL-IIR), chlorinated or brominated butyl rubber (Ce-IIR, Br-IIR), ethylene-propylene copolymer rubber (EPM), ethylene-propylene-diene monomer terpolymers (EPDMs), acrylonitrile-butadiene copolymer rubber (NBR), and hydrogenated NBR.
2o Illustrative of the additives are organic peroxide vulcanizer systems (organic peroxides, polyfunctional monomers, etc.), sulfur-containing vul-canizer systems (sulfur or sulfur-yielding compounds, zinc oxide, stearic acid, various vulcanization ac-celerators, etc.), reinforcing fillers, age resisters, and processing aids. Using a conventional mixer such as a roll mill, Banbury mixer or kneader, these addi-tives and the above-described rubber material are com-bined into a rubber mix, which is then used for the production of rubber closures.
Any plastic film can be used in the present in-vention insofar as it is inert to (is neither swollen by nor dissolved in) a liquid medicine filled in a prefilled syringe. Examples of the plastics can in-l0 elude polyethylene (ordinary molecular weight to ultra-high molecular weight), polypropylene, polycarbonates, polyesters, and fluorinated resins. Particularly preferred are fluorinated resins, including, for exam-ple, polytetrafluoroethylene (PTFE), tetrafluoro-ethylene-ethylene copolymer (ETFE), tetrafluoro-ethylene-hexafluoropropylene copolymer (FEP), tetrafluoroethylene-fluoroalkyl vinyl ether copolymers (PFAs), polyfluorinated vinylidene (PVDF), and polychlorotrifluoroethylene (PCTFE). These resins are used as sheets or films. No particular limitation is imposed on their thicknesses, but their thicknesses generally range from 1 to 500 ~m or so.
Each rubber closure according to the present in-vention is produced using the above-described mix rub-ber and plastic film, usually, by compression molding, but no particular limitation is imposed on its produc-tion method. Upon production by compression molding, for example, top and bottom mold members are used, which have been configured beforehand to define a predetermined shape therebetween. A mix rubber, which is in the form of a sheet and carries one or more plastic films laminated thereon at predetermined areas thereof or over the entire surface thereof, is placed on the lower mold member. The laminate is compressed to by the upper mold member and is then heated under elevated pressure to vulcanize the mix rubber, whereby a rubber closure is produced.
The present invention will hereinafter be de-scribed specifically by Examples and Comparative Exam-ples.
Examples 1-3 & Comparative Examples 1-4 (1) Production of rubber closures In each Example or Comparative Example, a rubber mix was prepared by mixing and kneading a rubber material and various additives in accordance with the corresponding formulation, which is shown in Table 1, by using a roll mill and an internal mixer. In each of Examples 1-3 and Comparative Examples 3-4, rubber closures for prefilled syringes were produced from this rubber mix and one or more fluorinated resin films (thickness: 50 Vim, resin type: ETFE resin) by compres sion molding. As is shown in Table 2, each of the rub ber closures was in a substantially cylindrical form having an average wall thickness of 4.2 mm, and was laminated with the fluorinated resin film at the entire inner walls) of its Luer-nozzle-receiving part or its Luer-nozzle-receiving part and Luer-lock-receiving part. In each of Comparative Examples 1-2, non-laminated rubber closures were also produced likewise as shown in Table 2. In all the Examples and Compara-tive Examples, the vulcanizing conditions were set at 150°C and 10 minutes.
With respect to the rubber closures so obtained, liquid leakage, gas sealing performance and eluting substance tests were conducted. Methods employed in these tests will be described subsequently herein.
Evaluation results are presented in Tables 3 to 5.

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(1) Liquid leakproofness test The liquid leakproofness of each rubber closure for a plastic-made prefilled syringe was evaluated fol-lowing Method 2 in Appendix D (Measurement of Self-sealing Degree) to the BS (British Standards).
1) Preparation of test samples Ten (10) plastic prefilled syringes of 10 mE ca-pacity were provided for the rubber closures obtained in each of the Examples and Comparative Examples. Each prefilled syringe was sealed at a position close to a flange thereof by a rubber-made plunger with a fluorinated resin film laminated on a surface thereof so that the internal capacity of its barrel became ap-proximately 10 mE. To seal the prefilled syringe, one of the rubber closures was fitted on its Luer nozzle.
2) Testing method Each syringe which had been prepared as a test sample in the above was immersed in a large beaker of 500 mt capacity filled with a 0.1 wt.~ aqueous solu-tion of methylene blue, with its Luer nozzle side directed downward. The beaker was placed in an autoclave and heated at 121°C for 30 minutes. After the autoclave was allowed to cool down, the syringe was taken out of the beaker. A sealing portion of the rub-ber closure was observed to determine whether or not it was contaminated with the blue color of methylene blue, whereby the existence or non-existence of leakage of the filled liquid was determined. The results are pre-sented in Table 3.
(2) Gas sealing performance test 1) Preparation of test samples Same as the preparation of test samples described above under (1)-1).
2) Evaluation test Each syringe was immersed in a beaker filled with a 5 wt.°s aqueous solution of glycerin, with its Luer nozzle size directed downward. The beaker with the syringe immersed therein was placed in a large vacuum desiccator. The desiccator was maintained at 20 torr (20 mmHg) for 30 minutes, during which the existence or non-existence of air leakage along the rubber closure was observed to evaluate its gas sealing performance.
The results are presented in Table 4.
(3) Eluting substance test The "testing method for plastic-made medicament containers" specified in Japanese Pharmacopoeia (JP
XIII) was followed.
1) Preparation of test solution For the rubber closures obtained in each of the Examples and Comparative Examples, twenty (20) clean syringes of the general purpose type, said syringes having 10 mE capacity, were provided. After each syringe was fitted with a rubber-made plunger of the same type as that descried above, 10 ml of commercial water for injections were injected and filled into the syringe through its Luer nozzle portion by using a com-mercial silicone-free disposable syringe. With the Luer nozzle side held up, the plunger was gently pushed to drive out air which remained in an end portion of the barrel. One of the rubber closures was fitted on the Luer nozzle to seal the syringe. With the Luer nozzle side held down, the syringe was maintained at 121°C for 1 hour in an autoclave to conduct elution.
2) Evaluation test Each test solution (200 mE), which had been prepared in accordance with the above-described proce-dures, was collected in a clean conical beaker. Fol-lowing the testing method for plastic-made medicament containers and the testing method for other aqueous in-jection containers set out in the Japanese Pharmacopoeia, the test solution was evaluated for changes in chemical properties. The results are pre-sented in Table 5.

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From the results presented in Table 5, the seal-ing rubber closures of the present invention laminated on the entire inner walls of the receiving parts there-of (Examples 1 and 2) are, different from the cor-responding non-laminated rubber closures (Comparative Examples 1 and 2), not observed to have substantially affected the liquid medicine (the commercial water for injections was used as the liquid medicine) by their chemical components. It is therefore evident that the sealing rubber closures according to the present inven-tion make it possible to minimize chemical influence which may be given to a medicament during a stability maintenance period (until a deadline for use). In this respect, the sealing rubber closures according to the present invention are the same as the conventional rub-ber closures having laminated films.
Concerning sealing performance which is an impor-tant functional requirement as containers for in-jectable preparations, it is also clear that the rubber closures according to the present invention are, owing to their shapes, superior in both the liquid leakproof-ness in Table 3 and the gas sealing performance in Table 4 to the rubber closures of the Comparative Exam-Ales.

Claims

1. A sealing rubber closure and syringe/container system including a sealing rubber closure and a syringe/container, the syringe/container being specified by ISO (the International Organization of Standardization) and having a Luer nozzle including a free end connected to a tapering cylindrical side wall which uniformly increases in diameter from said free end to a base of the Luer nozzle, said system comprising:
a Luer-nozzle-receiving part for receiving said Luer nozzle of said syringe/container, said Luer-nozzle-receiving part including a Luer-nozzle opening and inner and outer end portions, said inner-end portion being located opposite said Luer-nozzle-receiving opening and having an untapered, substantially cylindrical sidewall connected to an end wall, said outer-end portion being located adjacent to said Luer-nozzle-receiving opening and having first and second tapered, substantially cylindrical side walls, said first tapered, substantially cylindrical side wall connecting said untapered, substantially cylindrical side wall of said inner-end portion to said second tapered, substantially cylindrical side wall of said outer-end portion and said second tapered, substantially cylindrical side wall of said outer-end portion connecting said first tapered, substantially side wall to said Luer-nozzle-receiving opening, wherein when said Luer nozzle is inserted through said Luer-nozzle-receiving opening and is housed in said Luer-nozzle-receiving part, said untapered, substantially cylindrical side wall of said inner-end portion is in tight-fitting contact with said tapering cylindrical sidewall of said Luer nozzle because said tapering cylindrical sidewall of said Luer nozzle is of a slightly larger diameter than a diameter of said untapered, substantially cylindrical side wall of said inner-end portion of said Luer-nozzle-receiving part, said free end of said Luer nozzle is in approximate face-to-face contact with said end wall of said inner-end portion of said Luer-nozzle-receiving part, said first tapered, substantially cylindrical side wall of said outer-end portion is in approximate face-to-face contact with said tapering cylindrical side wall of said Luer nozzle because said first tapered, substantially cylindrical side wall of said outer-end portion has an approximate same degree of taper as the tapering cylindrical side wall of said Luer nozzle, and said second, substantially cylindrical side wall of said outer-end portion is in approximate face-to-face contact with a front end wall at said base of said Luer nozzle because said second tapered, substantially cylindrical side wall of said outer-end portion has an approximate same degree of taper as said front end wall at said base of said Luer nozzle; and a plastic film lamination our a surface of said Luer-nozzle-receiving part, wherein said free end of said Luer nozzle is to be maintained in contact with said plastic film lamination at said inner-end portion of said Luer-nozzle-receiving part of said sealing rubber closure.

2. The sealing rubber closure and syringe/container system according to claim 1, wherein said inner-end portion of said Luer-nozzle-receiving part of said sealing rubber closure has dimensions sufficient to receive at least one third of a length of said Luer nozzle.

3. The sealing rubber closure and syringe/container system according to claim 1 or 2, wherein at least one fourth of a length of said sealing rubber closure, as viewed in a direction upward from a lower end toward an upper end of said sealing rubber closure, is formed more resistant to deformation than a remaining portion thereof.

4. The sealing rubber closure and syringe/container system according to claim 1, 2 or 3, wherein a first area of said outer-end portion of said Luer-nozzle-receiving part which surrounds said Luer-nozzle-receiving opening is configured to have greater degree of taper than a second area of said outer-end portion adjacent to said inner-end portion of said Luer-nozzle-receiving part so that said basal end portion of said Luer nozzle is maintained to be in close contact with at least said second area of said outer-end portion of said Luer-nozzle-receiving part.

5. A sealing rubber closure and syringe/container system including a sealing rubber closure and a syringe/container, the syringe/container being specified by ISO (the International Organization of Standardization) and having a Luer nozzle including a free end connected to a tapering cylindrical side wall which uniformly increases in diameter from said free end to a base of the Luer nozzle, said system comprising:
a Luer-nozzle-receiving part for receiving said Luer nozzle of said syringe/container, said Luer-nozzle-receiving part including a Luer-nozzle-receiving opening and inner and outer end portions, said inner-end portion being opposite said Luer-nozzle-receiving opening and having an untapered, substantially cylindrical sidewall connected to an end wall, said outer-end portion being adjacent to said Luer-nozzle-receiving opening and having first and second tapered, substantially cylindrical side walls, said first tapered, substantially cylindrical side wall connecting said untapered, substantially cylindrical side wall of said inner-end portion to said second tapered, substantially cylindrical side wall of said outer-end portion and said second tapered, substantially cylindrical side wall of said outer end portion connecting said first tapered, substantially cylindrical side wall to said Luer-nozzle-receiving opening, wherein when said Luer nozzle is inserted through said Luer-nozzle-receiving opening and is housed in said Luer-nozzle-receiving prat, said untapered, substantially cylindrical side wall of said inner-end portion is in tight-fitting contact with said tapering cylindrical sidewall of said Luer nozzle because said tapering cylindrical sidewall of said Luer nozzle is of a slightly larger diameter than a diameter of said untapered, substantially cylindrical side wall of said inner-end portion of said Luer-nozzle-receiving part, said free end of said Luer nozzle is in approximate face-to-face contact with said end wall of said inner-end portion of said Luer-nozzle-receiving part, said first tapered, substantially cylindrical side wall of said outer-end pardon is in approximate face-to-face contact with said tapering cylindrical side wall of said Luer nozzle because said first tapered, substantially cylindrical side wall of said outer-end portion has an approximate same degree of taper as said tapering cylindrical side wall of said Luer nozzle, and said second, substantially cylindrical side wall of said outer-end portion is in approximate face-to-face contact with a front end wall at said base of said Luer nozzle because said second tapered, substantially cylindrical side wall of said outer-end portion has an approximate same degree of taper as said front end wall at said base of said Luer nozzle.

6. A sealing rubber closure and syringe/container system including a sealing rubber closure and a syringe/container, the syringe/container being specified by ISO (the International Organization of Standardization) and having a Luer nozzle and a Luer lock, the sealing rubber closure and syringe/container system comprising:
a Luer-nozzle-receiving part for receiving a top portion of a free end portion the Luer nozzle of the syringe/container, the Luer-nozzle-receiving part having an untapered, substantially cylindrical sidewall for tight-fitting contact against the top portion of the free end portion of a tapered, substantially cylindrical sidewall of the Luer nozzle of the syringe/container; and a Luer-lock-receiving part including a receiving opening and inner and outer end portions, the inner-end portion of the Luer-lock-receiving part being located opposite the receiving opening of the Luer-lock-receiving part and being located adjacent to the Luer-nozzle-receiving part, the outer-end portion of the Luer-lock-receiving part being located adjacent to the receiving opening of the Luer-lock-receiving part, the inner-end portion of the Luer-lock-receiving part having an untapered, substantially cylindrical sidewall for tight-fitting contact against at least an inner-end portion of an untapered, substantially cylindrical sidewall of a free end portion of the Luer lock of the syringe/container when the Luer nozzle and the Luer lock of the syringe/container are both inserted through the receiving opening of the Luer-lock-receiving part and are housed in the Luer-nozzle-receiving part and the Luer-lock-receiving part, respectively, and the outer-end portion of: the Luer-lock-receiving part having at least a tapered, substantially cylindrical sidewall for face-to-face contact against a basal-end portion of the Luer nozzle and the Luer lock of the syringe/container when the Luer nozzle and the Luer lock of the syringe/container are both inserted through the receiving opening of the Luer-lock-receiving part and are housed in the Luer-nozzle-receiving part and the Luer-lock-receiving part, respectively.

7. The sealing rubber closure and syringe/container system according to claim 6, wherein the inner-end portion of the Luer-lock-receiving part, which has the untapered, substantially cylindrical sidewall, has dimensions sufficient to receive at least one third of a length of the Luer lock.

8. The sealing rubber closure arid syringe/container system according to claim 6 or 7, wherein said Luer-lock-receiving part is provided on a side of the inner-end portion thereof with a ridge which is to be inserted tightly in a space between the Luer lock and the Luer nozzle of the syringe/container,

9. The sealing rubber closure and syringe/container system according to claim 6, 7 or 8, further comprising a plastic film lamination on a surface of the Luer-lock-receiving part, wherein the free-end portion of the Luer lock is to be maintained in contact with the plastic film lamination at the inner end portion of the Luer-lock-receiving part of the sealing rubber closure.

10. The sealing rubber closure and syringe/container system according to any one of claims 6 to 9, wherein the outer-end portion of the Luer-lock-receiving part is comprised of first and second sections, the first section being adjacent to the receiving opening and having a tapered, substantially cylindrical sidewall, the second section being adjacent to the inner-end portion of the Luer-lock-receiving part and having a tapered, substantially cylindrical sidewall which has a degree of taper less than a degree of taper of the tapered, substantially cylindrical sidewall of the first section of the outer-end portion of Luer-lock-receiving part.

11. The sealing rubber closure and syringe/container system according to claim 10, wherein the tapered, substantially cylindrical sidewall of the first section of the outer-end portion of the Luer-lock-receiving part is approximately parallel to a basal-end portion of the free end portions of the Luer nozzle and the Luer lock when the Luer nozzle and the Luer lock are inserted through the receiving opening so that the Luer nozzle and Luer lock are housed in the Luer-nozzle-receiving part and the Luer-lock-receiving part, respectively.

12. The sealing rubber closure and syringe/container system according to claim 11, wherein the tapered, substantially cylindrical sidewall of the second section of the outer-end portion of the Luer-lock-receiving part is slightly tapered with respect to the untapered, substantially cylindrical sidewall of the free-end portion of the Luer lock when the Luer nozzle and the Luer lock are inserted through the receiving opening so that the Luer nozzle and Luer lock are housed in the Luer-nozzle-receiving part and the Luer-lock-receiving part, respectively.

13. The sealing rubber closure and syringe/container system according to claim 12, further comprising a rounded portion located between the first and second sections.

14, The sealing rubber closure and syringe/container system according to claim 8, wherein the ridge extends into the Luer-lock-receiving part. from a wall approximately perpendicular to the untapered, substantially cylindrical sidewall of the inner-end portion of the Luer-lock-receiving part.

15. A sealing rubber closure and syringe/container system including a sealing rubber closure and a syringe/container, the syringe/container being specified by ISO (the International Organization of Standardization) and having a Luer nozzle and a Luer lock, the sealing rubber closure and syringe/container system comprising:
a Luer-lock-receiving part having a Luer-lock-receiving opening, an inner-end portion opposite the Luer-lock-receiving opening, and an outer-end portion adjacent to the Luer-lock-receiving opening, the outer-end portion having a first area adjacent to the Luer-lock-receiving opening and a second area adjacent to the inner-end portion of the Luer-lock-receiving part, the first area having a tapered, substantially cylindrical sidewall which has a greater degree of taper than a tapered, substantially cylindrical sidewall of the second area so that the tapered, substantially cylindrical sidewall of the first area is maintained in close contact with an outer surface of a basal end of the Luer nozzle and the Luer lock of the syringe/container and the tapered, substantially cylindrical sidewall of the second area is maintained in close contact with an outer-end portion of an untapered, substantially cylindrical sidewall of the Luer-lock.

16. A sealing rubber closure for sealingly closing a Luer-nozzle and Luer-lock of a syringe/container, the syringe/container being specified by ISO (the International Organization of Standardization), the sealing rubber closure comprising:
a receiving opening for receiving the Luer nozzle and the Luer-lock of the syringe container; and a Luer-nozzle-and-Luer-lock-receiving recess located adjacent to the receiving opening, the Luer-nozzle-and-Luer-lock-receiving recess having first, second and third sections, the first section of the Luer-nozzle-and-Luer-lock-receiving recess having at least one tapered, substantially cylindrical sidewall with a first end connected to an outer periphery of the receiving opening and a second end connected to a first end of an untapered, substantially cylindrical sidewall of the second section of the Luer-nozzle-and-Luer-lock-receiving recess, the second end of the untapered, substantially cylindrical sidewall of the second section of the Luer-nozzle-and-Luer-lock-receiving recess being connected to a first end of an approximately annular wall which is perpendicular to the untapered, substantially cylindrical sidewall of the second section, the third section of the Luer-nozzle-and-Luer-lock-receiving recess having an untapered, substantially cylindrical sidewall having a first end which is connected to a second end of the approximately annular wall of the second section and a second end which is connected to an approximately circular wall which is perpendicular to the untapered, substantially cylindrical sidewall of the third section of the Luer-nozzle-and-Luer-lock-receiving recess.

17. The sealing rubber closure according to claim 16, further comprising a plastic film lamination laminated on the tapered, substantially cylindrical of the first section of the Luer-nozzle-and-Luer-lock-receiving recess and on the untapered, substantially cylindrical sidewall of the second section of the Luer-nozzle-and-Luer-lock-receiving recess.

18. The sealing rubber closure according to claim 16 or 17, wherein the at least one tapered, substantially cylindrical sidewall of the first section of the Luer-nozzle-and-Luer-lock-receiving recess has only a very slight degree of taper so that the tapered substantially cylindrical sidewall is only slightly slanted with respect to the untapered, substantially cylindrical sidewall of the second section of the Luer-nozzle-and-Luer-lock-receiving recess.

19. The sealing rubber closure according to claim 16 or 17, wherein the at least one tapered, substantially cylindrical sidewall of the first section of the Luer-nozzle-and-Luer-lock-receiving recess has a very high degree of taper so that the tapered, substantially cylindrical sidewall is very slanted with respect to the untapered, substantially cylindrical sidewall of the second section of the Luer-nozzle-and-Luer-lock-receiving recess.

20. The sealing rubber closure according to claim 19, further comprising a cylindrical ridge connected to the approximately annular wall of the second section and extending into the Luer-nozzle-and-Luer-lock-receiving recess.

21. The sealing rubber closure according to claim 16 or 17, wherein the at least one tapered, substantially cylindrical sidewall of the first section of the Luer-nozzle-and-Luer-lock-receiving recess is actually first and second tapered, substantially cylindrical sidewalls connected to each other, the first tapered, substantially cylindrical sidewall having a very high degree of taper, and the second tapered, substantially cylindrical sidewall having only a very slight degree of taper so that the second tapered, substantially cylindrical sidewall is only slightly slanted with respect to the untapered, substantially cylindrical sidewall of the second section of the Luer-nozzle-and-Luer-lock-receiving recess.

22. The sealing rubber closure according to claim 21, further comprising a cylindrical ridge connected to the approximately annular wall of the second section and extending into the Luer-nozzle-and-Luer-lock-receiving recess.